rs67736127

Positions:

• chr13-103052782-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000452.3(SLC10A2):​c.497-74C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 926,222 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (59 hom., cov: 32)
  • Exomes 𝑓: 0.018 (203 hom.)
• Consequence: SLC10A2 NM_000452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

Genes affected

SLC10A2 (HGNC:10906): (solute carrier family 10 member 2) This gene encodes a sodium/bile acid cotransporter. This transporter is the primary mechanism for uptake of intestinal bile acids by apical cells in the distal ileum. Bile acids are the catabolic product of cholesterol metabolism, so this protein is also critical for cholesterol homeostasis. Mutations in this gene cause primary bile acid malabsorption (PBAM); muatations in this gene may also be associated with other diseases of the liver and intestines, such as familial hypertriglyceridemia (FHTG). [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0246 (3741/152162) while in subpopulation AFR AF= 0.0371 (1540/41534). AF 95% confidence interval is 0.0355. There are 59 homozygotes in gnomad4. There are 1733 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3741 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC10A2	NM_000452.3	c.497-74C>A		intron_variant		ENST00000245312.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC10A2	ENST00000245312.5	c.497-74C>A		intron_variant		1	NM_000452.3	P1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3741 AN: 152044 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.0183 AC: 14171 AN: 774060 Hom.: 203 AF XY: 0.0180 AC XY: 7400 AN XY: 411432

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.00931

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.0000276

Gnomad4 SAS exome AF: 0.00455

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0197

Gnomad4 OTH exome AF: 0.0221

GnomAD4 genome AF: 0.0246 AC: 3741 AN: 152162 Hom.: 59 Cov.: 32 AF XY: 0.0233 AC XY: 1733 AN XY: 74382

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0128

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00333

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0260 Hom.: 16

Bravo AF: 0.0251

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs67736127; hg19: chr13-103705132;